Transcript Chapter 8 notes

Chapter 8
An Introduction to
Metabolism
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: The Energy of Life
• The living cell is a miniature chemical factory
where thousands of reactions occur
• The cell extracts energy and applies energy to
perform work
• Some organisms even convert energy to light, as
in bioluminescence
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 8.1: An organism’s metabolism transforms matter
and energy, subject to the laws of thermodynamics
• Metabolism is the totality of an organism’s
chemical reactions
• Metabolism is an emergent property of life that
arises from interactions between molecules within
the cell
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Organization of the Chemistry of Life into
Metabolic Pathways
• A metabolic pathway begins with a specific
molecule and ends with a product
• Each step is catalyzed by a specific enzyme
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LE 8-UN141
Enzyme 1
A
B
Reaction 1
Starting
molecule
Enzyme 2
Enzyme 3
D
C
Reaction 2
Reaction 3
Product
• Catabolic pathways release energy by breaking
down complex molecules into simpler compounds
• Anabolic pathways consume energy to build
complex molecules from simpler ones
• Bioenergetics is the study of how organisms
manage their energy resources
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Forms of Energy
• Energy is the capacity to cause change
• Energy exists in various forms, some of which can
perform work
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• Kinetic energy is energy associated with motion
– Heat (thermal energy) is kinetic energy associated
with random movement of atoms or molecules
• Potential energy is energy that matter possesses
because of its location or structure
– Chemical energy is potential energy available for
release in a chemical reaction
• Energy can be converted from one form to another
Animation: Energy Concepts
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LE 8-2
On the platform,
the diver has
more potential
energy.
Diving converts
potential
energy to
kinetic energy.
Climbing up converts
kinetic energy of
muscle movement to
potential energy.
In the water, the
diver has less
potential energy.
The Laws of Energy Transformation
• Thermodynamics is the study of energy
transformations
• A closed system, such as that approximated by
liquid in a thermos, is isolated from its
surroundings
• In an open system, energy and matter can be
transferred between the system and its
surroundings
• Organisms are open systems
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The First Law of Thermodynamics
• According to the first law of thermodynamics, the
energy of the universe is constant
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
• The first law is also called the principle of
conservation of energy
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The Second Law of Thermodynamics
• During every energy transfer or transformation,
some energy is unusable, often lost as heat
• According to the second law of thermodynamics,
every energy transfer or transformation increases
the entropy (disorder) of the universe
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LE 8-3
Heat
Chemical
energy
First law of thermodynamics
CO2
H2O
Second law of thermodynamics
• Living cells unavoidably convert organized forms
of energy to heat
• Spontaneous processes occur without energy
input; they can happen quickly or slowly
• For a process to occur without energy input, it
must increase the entropy of the universe
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Biological Order and Disorder
• Cells create ordered structures from less ordered
materials
• Organisms also replace ordered forms of matter
and energy with less ordered forms
• The evolution of more complex organisms does
not violate the second law of thermodynamics
• Entropy (disorder) may decrease in an organism,
but the universe’s total entropy increases
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Concept 8.2: The free-energy change of a reaction tells
us whether the reaction occurs spontaneously
• Biologists want to know which reactions occur
spontaneously and which require input of energy
• To do so, they need to determine energy changes
that occur in chemical reactions
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Free-Energy Change, G
• A living system’s free energy is energy that can do
work when temperature and pressure are uniform,
as in a living cell
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• The change in free energy (∆G) during a process
is related to the change in enthalpy, or change in
total energy (∆H), and change in entropy (T∆S):
∆G = ∆H - T∆S
• Only processes with a negative ∆G are
spontaneous
• Spontaneous processes can be harnessed to
perform work
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Free Energy, Stability, and Equilibrium
• Free energy is a measure of a system’s instability,
its tendency to change to a more stable state
• During a spontaneous change, free energy
decreases and the stability of a system increases
• Equilibrium is a state of maximum stability
• A process is spontaneous and can perform work
only when it is moving toward equilibrium
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LE 8-5
Gravitational motion
Diffusion
Chemical reaction
Free Energy and Metabolism
• The concept of free energy can be applied to the
chemistry of life’s processes
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Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction proceeds with a net release
of free energy and is spontaneous
• An endergonic reaction absorbs free energy from
its surroundings and is nonspontaneous
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LE 8-6a
Free energy
Reactants
Amount of
energy
released
(G < 0)
Energy
Products
Progress of the reaction
Exergonic reaction: energy released
LE 8-6b
Free energy
Products
Energy
Reactants
Progress of the reaction
Endergonic reaction: energy required
Amount of
energy
required
(G > 0)
Equilibrium and Metabolism
• Reactions in a closed system eventually reach
equilibrium and then do no work
• Cells are not in equilibrium; they are open systems
experiencing a constant flow of materials
• A catabolic pathway in a cell releases free energy
in a series of reactions
• Closed and open hydroelectric systems can serve
as analogies
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LE 8-7a
G < 0
A closed hydroelectric system
G = 0
LE 8-7b
G < 0
An open hydroelectric system
LE 8-7c
G < 0
G < 0
G < 0
A multistep open hydroelectric system
Concept 8.3: ATP powers cellular work by coupling
exergonic reactions to endergonic reactions
• A cell does three main kinds of work:
– Mechanical
– Transport
– Chemical
• To do work, cells manage energy resources by
energy coupling, the use of an exergonic process
to drive an endergonic one
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The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy
shuttle
• ATP provides energy for cellular functions
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LE 8-8
Adenine
Phosphate groups
Ribose
• The bonds between the phosphate groups of
ATP’s tail can be broken by hydrolysis
• Energy is released from ATP when the terminal
phosphate bond is broken
• This release of energy comes from the chemical
change to a state of lower free energy, not from
the phosphate bonds themselves
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LE 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O
Pi
+
Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
+
Energy
• In the cell, the energy from the exergonic reaction
of ATP hydrolysis can be used to drive an
endergonic reaction
• Overall, the coupled reactions are exergonic
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LE 8-10
Endergonic reaction: G is positive, reaction
is not spontaneous
NH2
Glu
+
NH3
Ammonia
Glutamic
acid
G = +3.4 kcal/mol
Glu
Glutamine
Exergonic reaction: G is negative, reaction
is spontaneous
ATP
+
H2O
ADP
Coupled reactions: Overall G is negative;
together, reactions are spontaneous
+
Pi
G = –7.3 kcal/mol
G = –3.9 kcal/mol
How ATP Performs Work
• ATP drives endergonic reactions by
phosphorylation, transferring a phosphate group to
some other molecule, such as a reactant
• The recipient molecule is now phosphorylated
• The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 8-11
Pi
P
Motor protein
Protein moved
Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
Pi
ATP
Pi
P
Solute transported
Solute
Transport work: ATP phosphorylates transport proteins
P
NH2
Glu
+
NH3
+
Pi
Glu
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made
Chemical work: ATP phosphorylates key reactants
The Regeneration of ATP
• ATP is a renewable resource that is regenerated
by addition of a phosphate group to ADP
• The energy to phosphorylate ADP comes from
catabolic reactions in the cell
• The chemical potential energy temporarily stored
in ATP drives most cellular work
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 8-12
ATP
Energy for cellular work
(endergonic, energyconsuming processes)
Energy from catabolism
(energonic, energyyielding processes)
ADP +
P
i
Concept 8.4: Enzymes speed up metabolic
reactions by lowering energy barriers
• A catalyst is a chemical agent that speeds up a
reaction without being consumed by the reaction
• An enzyme is a catalytic protein
• Hydrolysis of sucrose by the enzyme sucrase is an
example of an enzyme-catalyzed reaction
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LE 8-13
Sucrose
C12H22O11
Glucose
C6H12O6
Fructose
C6H12O6
The Activation Energy Barrier
• Every chemical reaction between molecules
involves bond breaking and bond forming
• The initial energy needed to start a chemical
reaction is called the free energy of activation, or
activation energy (EA)
• Activation energy is often supplied in the form of
heat from the surroundings
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LE 8-14
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
G < O
C
D
Products
Progress of the reaction
How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA
barrier
• Enzymes do not affect the change in free-energy
(∆G); instead, they hasten reactions that would
occur eventually
Animation: How Enzymes Work
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 8-15
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
Course of
reaction
with enzyme
G is unaffected
by enzyme
Products
Progress of the reaction
Substrate Specificity of Enzymes
• The reactant that an enzyme acts on is called the
enzyme’s substrate
• The enzyme binds to its substrate, forming an
enzyme-substrate complex
• The active site is the region on the enzyme where
the substrate binds
• Induced fit of a substrate brings chemical groups
of the active site into positions that enhance their
ability to catalyze the reaction
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LE 8-16
Substrate
Active site
Enzyme
Enzyme-substrate
complex
Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to
the active site
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
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LE 8-17
Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
Substrates
Enzyme-substrate
complex
Active
site is
available
for two new
substrate
molecules.
Enzyme
Products are
released.
Substrates are
converted into
products.
Products
Active site (and R groups of
its amino acids) can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
Effects of Local Conditions on Enzyme Activity
• An enzyme’s activity can be affected by:
– General environmental factors, such as
temperature and pH
– Chemicals that specifically influence the
enzyme
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Effects of Temperature and pH
• Each enzyme has an optimal temperature in which
it can function
• Each enzyme has an optimal pH in which it can
function
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LE 8-18
Optimal temperature for
typical human enzyme
0
Optimal temperature for
enzyme of thermophilic
(heat-tolerant
bacteria)
40
60
Temperature (°C)
20
80
100
Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
0
1
2
3
4
Optimal pH
for trypsin
(intestinal
enzyme)
5
pH
Optimal pH for two enzymes
6
7
8
9
10
Cofactors
• Cofactors are nonprotein enzyme helpers
• Coenzymes are organic cofactors
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Enzyme Inhibitors
• Competitive inhibitors bind to the active site of an
enzyme, competing with the substrate
• Noncompetitive inhibitors bind to another part of
an enzyme, causing the enzyme to change shape
and making the active site less effective
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LE 8-19
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Competitive
inhibitor
Competitive inhibition
A noncompetitive
inhibitor binds to the
enzyme away from the
active site, altering the
conformation of the
enzyme so that its
active site no longer
functions.
Noncompetitive inhibitor
Noncompetitive inhibition
Concept 8.5: Regulation of enzyme activity helps
control metabolism
• Chemical chaos would result if a cell’s metabolic
pathways were not tightly regulated
• To regulate metabolic pathways, the cell switches
on or off the genes that encode specific enzymes
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Allosteric Regulation of Enzymes
• Allosteric regulation is the term used to describe
cases where a protein’s function at one site is
affected by binding of a regulatory molecule at
another site
• Allosteric regulation may either inhibit or stimulate
an enzyme’s activity
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Allosteric Activation and Inhibition
• Most allosterically regulated enzymes are made
from polypeptide subunits
• Each enzyme has active and inactive forms
• The binding of an activator stabilizes the active
form of the enzyme
• The binding of an inhibitor stabilizes the inactive
form of the enzyme
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 8-20a
Allosteric enzyme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Oscillation
Nonfunctional
active site
Allosteric activator
stabilizes active form.
Inactive form
Stabilized active form
Allosteric inhibitor
stabilizes inactive form.
Inhibitor
Allosteric activators and inhibitors
Stabilized inactive
form
• Cooperativity is a form of allosteric regulation that
can amplify enzyme activity
• In cooperativity, binding by a substrate to one
active site stabilizes favorable conformational
changes at all other subunits
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LE 8-20b
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Stabilized active form
Cooperativity another type of allosteric activation
Feedback Inhibition
• In feedback inhibition, the end product of a
metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting
chemical resources by synthesizing more product
than is needed
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LE 8-21
Initial substrate
(threonine)
Active site
available
Isoleucine
used up by
cell
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Feedback
inhibition
Enzyme 2
Active site of
enzyme 1 can’t
bind
Intermediate B
theonine
pathway off
Enzyme 3
Isoleucine
binds to
allosteric
site
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
Specific Localization of Enzymes Within the Cell
• Structures within the cell help bring order to
metabolic pathways
• Some enzymes act as structural components of
membranes
• Some enzymes reside in specific organelles, such
as enzymes for cellular respiration being located
in mitochondria
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LE 8-22
Mitochondria,
sites of cellular respiration
1 µm